Programmable patterning and masking array for corneal collagen crosslinking

ABSTRACT

The present application relates generally to a method for vision correction using corneal collagen crosslinking (“CCXL”), in which the physician is able to precisely control the pattern of ultraviolet (“UV”) energy delivered to the cornea, by means of a programmable masking array placed between the UV source and the cornea. A CCXL LCD masked is used to create various patterns of “on” and “off” pixels. The physician is able to control the degree of polarization of the LCD pixels, thereby allowing the physician to create various patterns of UV irradiation and thus, varying levels of CCXL.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional application of U.S. patentapplication Ser. No. 14/751,358, filed Jun. 26, 2015, which applicationclaims the benefit of the filing date of U.S. Provisional PatentApplication No. 62/018,943, filed Jun. 30, 2014, the disclosures of theforegoing applications are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

Corneal collagen crosslinking (CCXL) has been used since the late 1990sto treat keratoconus. Recently it has been applied to healthy eyes toaffect refractive changes in the shape of the cornea, and to eyes withcertain antibiotic resistive infections.

The standards of corneal collagen crosslinking for treatment ofkeratoconus set the dose at an energy per area of 3 mW/cm2, delivereduniformly over the center 8 mm of the cornea for 30 minutes. This sumsto about 5.4 J/cm2 of energy, or a total of about 2.7 J. However, thegoals of CCXL for refractive correction (and anti-infective use) aredifferent than that of keratoconus treatment, and thus the dosimetry,typically differ from this standard protocol.

CCXL for vision correction achieves refractive shape change of thecornea by creating chemical bonds between the protein layers in thecorneal stroma. These bonds (crosslinks) increase the stiffness of thecornea in the region crosslinked. This increased stiffness changes thebalance between the cornea tension and the intraocular pressure. Throughmechanisms not completely understand in the industry, within a few daysof CCXL therapy, physiologic processes reshape the cornea. The amount ofreshaping, and thus the degree of curvature correction, is determined bya number of treatment parameters, including the amount and rate ofenergy delivery, the treatment time, and the shape and size of thetreated area on the cornea. For myopia (nearsightedness), the center ofthe cornea is stiffened; for hyperopia (farsightedness), an annulusaround the periphery of the cornea is stiffened. For more complicatedcorrections such as astigmatism, custom patterns are used.

Currently, there exists a a fixed optical mask that is placed on thecornea in the form of an etched contact lens patterned to spatiallymodulate the UV dose delivered across the cornea. However, by thismethod, a custom-etched contact lens would have to be provided for eachindividualized patient prescription.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagrammatic sectional view of a device according to oneembodiment of the invention.

FIG. 2 is a diagrammatic perspective view of a device according to afurther embodiment of the invention.

FIG. 3 is a diagrammatic perspective view of a device according to afurther embodiment of the invention.

FIG. 4 is a diagrammatic plan view depicting an element used in certainembodiments of the invention.

FIG. 5 is a diagrammatic plan view depicting an element used in otherembodiments of the invention.

DETAILED DESCRIPTION

One aspect of the invention described herein provides a method toprecisely control the pattern of UV energy delivered to the corneaduring the crosslinking procedure by means of a programmable maskingarray placed between the UV source and the cornea. Preferred methods andapparatus according to this aspect of the present invention accomplishesthe masking in a controllable manner, creating programmable patterns onthe contact lens using technologies typically employed in imagedisplays. The mask patterns can be customized in real time, and can evenbe varied throughout the CCXL treatment if necessary as regions reachthe desired amount of crosslinking. This customized or ‘live’ mask canprovide real time 3 dimensional control of administered dose (X, Y, andtime) across the corneal surface. The customization optionally can becoupled with a point by point feedback system (i.e., acoustic or opticalspectral reflected spectral analysis) that is capable of monitoring thedegree of cross-linking achieved at multiple points in the cornea duringthe CCXL treatment. One form of feedback system capable of providingsuch monitoring is disclosed in the commonly assigned U.S. ProvisionalPatent Application entitled “Real Time Acoustic Dosimetry For CornealCollagen Crosslinking,” filed on Jun. 27, 2014, which is incorporated inthis application in its entirety.

Apparatus according to one aspect of the invention utilizes a thin arrayof liquid crystal display (LCD) “pixels.” The array consists of a layerof liquid crystals that are able to change the polarization of lightpassing through them, sandwiched between two orthogonal polarizers and apatterned electrode array to control the degree of polarization of theliquid crystals. Unlike most modern image displays, the CCXL maskpresented here does not employ an array of colored sub pixels; it ismonochromatic, effectively transparent, or black. In one embodiment,twisted nematic liquid crystals are used to rotate the polarization ofthe light passing through; however, other types of liquid crystals, withdifferent mechanisms of interaction with the polarization of theincident light can also be employed as UV masks. As some liquid crystalsare damaged by UV exposure, and others are non-transparent to UV even inthe “on” state, care must be taken to select materials that willfunction appropriately. There are factors working in favor of areasonably broad field of liquid crystal material selection for thoseskilled in the art such as the facts that the CCXL procedure is neithervery long (typically under 30 min), nor very high intensity UV(typically 3 mW/cm2 to 30 mW/cm2). Additionally, the wavelength used islong or UV, around 360 nm to 380 nm, thus comparatively low energy.

In its simplest embodiment, the LCD mask presented herein is used inconjunction with a standoff UV source. In this approach, UV light isgenerated a few centimeters away from the target eye with the LCDmasking contact lens in place. Light generated at a distance from theeye provides roughly collimated rays impinging on the eye, so theplanned crosslinking treatment pattern can be mimicked in theprogrammable mask pattern. The pixels of the masking array can becontrolled over a given dynamic range of light transmission bymanipulating the degree of polarization of the liquid crystals, goingfrom full dark to fully transparent, enabling a customized CCXL patternto be created on the eye from essentially a uniformly flooding UVsource.

One of the challenges of a stand-off UV source for CCXL is patientmotion. By using this on cornea mask with a standoff light source, it ispossible to use some or all of the LCD pixel pattern as fiducial marksfor a UV light alignment system. If, for example, the LCD were patternedonto a scleral type contact lens □ a lens design that moves veryminimally with respect to the corneal surface □ CCXL UV delivery systememploying a stand off UV source that was able to move in X and Y (withthe optical axis of the eye as Z) could be coupled with an imaging andanalysis approach to move the UV source in response to gross patientmovements during the procedure. The area flooded with UV would track theLCD pattern, limiting UV exposure to areas other than the target regionon the cornea.

Another significant drawback of stand-off UV sources is the need for thepatient to have the eyelid of the target eye retracted with a speculum.Along the same lines as fiducial markers to track motion, specificallydesigned LCD pixel patterns outside the area of UV irradiation can beused as a blink detectors for non-speculum CCXL procedures with a standoff light. Once the mask lens is in place on the eye, pixels outsidetreatment region that are very near the eyelids (particular to thatpatient, as everyone's eyelids are different) could be darkened. If theimage capture system fails to “see” one of these marks during theprocedure, the eyelid must be closing, and the UV can be shut off.

The more preferred embodiment of the LCD mask is to be built into anon-eye CCXL UV delivery device. Such devices are taught in Chuck et al.,U.S. Patent Application Publication No. 2013/0211389 A1 (“Chuck”); inCooper et al., U.S. Provisional Patent Application No. 61/839,016, filedJun. 25, 2013 (“Cooper '016”); and in Cooper et al., U.S. patentapplication Ser. No. 14/314,518, filed Jun. 25, 2014 (“Cooper '518”),the disclosures of which are incorporated herein. Certain devicesaccording to Cooper '016 and '518 and Chuck have form and size similarto that of a conventional contact lens.

In certain embodiments disclosed in Cooper '016 and '518, a uniform UVback light is created by directing light into a dispersive element suchas a plastic or silicone material bulk loaded with very small UVscattering particles. The dispersive element may be in the form of alayer or shell with an inner surface facing toward the eye and an outersurface facing away from the eye, and with edge surfaces extendingbetween the inner and outer surfaces. Light may be supplied to thedispersive element by emitters such as LEDs mounted to the structureitself or by a transmission fiber extending to the structure from alight source remote from the eye. No additional light diffusers arenecessary with this backlight method. In other embodiments, thedispersive element may include a total internal reflector formed from atransparent material with numerous reflecting points such as features inone or more surfaces of the element as, for example, in the outersurface of the element facing away from the eye. A dispersive element ofthis type may be similar to the elements used in backlighting in modernvideo monitors. Typically, a further light diffuser is used inconjunction with a dispersive element of this type.

One challenge of effectively masking “on-lens” generated UV lightcreated with an edge light system (with either reflective diffusers orwith the bulk scatter approach) is the fact that light rays created arenot collimated, and thus on a curved lens, a mask may not be exceedinglyeffective at preventing UV exposure to areas of the cornea directlybelow the mask. This is the parallax problem displayed in FIG. 1.

There are a number of ways to address the parallax issue. Easiest is anembodiment where the internal reflecting light guide that carries thelight from the edge source is extremely thin. In Cooper '016 and '518,this means no thicker than the diameter of a single fiber optic fiber.With an LED perimeter array, the die size and orientation of the LEDswill dictate the minimum thickness. It is easy to see from FIG. 1 thatthe thinner the scatterer, the less parallax comes into play.

A second parallax defeating measure, preferably used in conjunction witha thin internal reflective light guide, is a collimator. These devicesare typically used as “privacy filters” on laptop displays. They preventa viewer from looking at information displayed on the screen form theside. Most common is the “microlouver” technology from 3M. There are twoapproaches to using this privacy technology as a collimator to eliminatethe parallax challenge to UV masking for CCXL. In one embodiment, themicrolouver device would essentially be mounted “inside out,” above (onthe outer or eyelid side) of the LCD mask, between the LCD mask and thescattering internal reflector. Mounting the privacy louver “inside out”means that the face of the louver that would typically face out towardthe eye of the viewer (of the display screen for which they wereoriginally designed) is turned to face toward the light guide (away fromthe eye of the patient). In this manner, only light that scattersperpendicular to the plane of the LCD (or normal to the sphericalsurface if the LCD is curved) is allowed to pass through the collimatorto in turn either hit the cornea or be blocked by the mask. Thiseliminates light rays from the side that could get around the mask andwill provide very precise boundaries between “on” pixels and “off”pixels. Effectively, this is a high-pass spatial filter.

The potential problem with this inside-out approach is attenuation ofthe UV light. Depending on the desired UV intensity in the non-maskedareas, an ordered optical stack of “light guide to collimator to mask”may reduce the therapeutic UV intensity out of the desired range. Thepolarizing filters on the LCD itself can further attenuate the scatteredlight energy coming out of the light guide. Modern LCDs deal with thisattenuation by using a reflective polarizer between the light guide andthe liquid crystals. With a reflective polarizer, the light that is“off-polarization” from the filter is reflected back into the lightguide to be rescattered and given a second chance (and third, fourth,etc.) at arriving at the polarizer with the correct polarization.

An alternative approach to help mitigate this attenuation is to use theprivacy filter as designed, layering it on the front or inner a side ofthe LCD mask, i.e., the side of the LCD mask facing toward the cornea.In this embodiment, correctly polarized light from scatterers that arenot directly above the LCD pixel can enter the LCD mask, increasing thebrightness coming out of the “on” pixels. The trade-off is that thespatial bandpass frequency has been lowered to some degree with“off-axis” rays able to enter the LCD. These rays will blur the linebetween “on” and “off” pixels, effectively reducing the contrast. Thecloser the LCD mask is to the corneal surface, the less this blurringwill be. Given that the CCXL procedure is based on the creation ofreactive free radical species in the cornea, and that the diffusiondistances of these species during the treatment time is currentlyunknown in the field (but likely not to be extremely short), someblurring of the crosslinking effect at the pixel boundaries is likelyanyway due to the fundamental physiology of the procedure. Asunderstanding of this phenomenon improves, it may become more criticalto tightly control the spatial frequency capabilities of the mask/filterarrangement. Alternatively, it may become apparent that some blurring ofthe lines do to off-axis rays is totally acceptable.

Brightness enhancer films can be employed to direct the scattered lightforward. This approach can exceed collimators in terms of the amount oflight it lets through. Enhancer films use tiny prisms to redirect(refract) the light rays from the backlight, emitting them directionallytoward the observer. While not true collimation, these enhancers reducethe parallax problem significantly without losing brightness. Foroperation in UV, these enhancers can be made very thin. One type ofenhancer film incorporates an array of prisms extending parallel to oneanother. These prisms are arranged to narrow the spreading angle oflight in one plane. In one embodiment, two such enhancers are arrangedso that their narrowing planes are orthogonal to one another. The twoorthogonal enhancers are placed between the dispersive element and thereflective polarizer of the LCD. This optical stack should exhibit aslightly lower frequency cut-off for spatial resolution (meaning someadditional blurring of “on” and “off”) than either of the microlouvercollimator embodiments, but will provide much more light to the cornea.

The LCD mask can be used to create various patterns of “on” and “off”pixels. These pixels are programmable in that they can be turned “on”(transparent) or “off” (black) at any point before or during theprocedure. The pixels can also be controlled to be partially “on” or“off” by modulating the control voltage levels in either active mode(with thin film transistors, as used in most modern mobile technologyscreens) or passive mode (a simple conductor grid used on most older LCDvideo display screen). Passive LCD displays have fallen out of favor dueto slow refresh rates and poor viewing angles, neither of which areconcerns for a CCXL LCD mask.

These aspects of spatial and intensity control allow the physician tocreate various patterns of UV irradiation (and thus varying levels ofcorneal collagen crosslinking) on the cornea to affect the desiredtherapeutic outcome, be that corneal stability, corneal shape change,anti-infection care, or treatment of other corneal maladies. In oneembodiment for the treatment of myopia and hyperopia, the pixels arearranged in an annular pattern, with a center circle, and surroundingannular rings. For one particular case, the center pixel is set toapproximately 1 mm in diameter, with 7 surrounding ½ mm wide annularrings, for a total of 8 pixel elements. For treatment of myopia, thecenter pixel or pixels (depending on the physician defined prescription)would be “on,” allowing UV to pass through, and the peripheral ringswould be “off,” limiting the size of the CCXL spot in the center of thecorneal. (FIG. 2.)

Various methods can be used to determine the size of the CCXL spot, someof these based on modifications of the Munnerlyn formula used in laserablative corneal correction. For treatment of hyperopia, the oppositepattern of “on” and “off” pixels would be created, with the centerpixels “off” (black) and the outer rings “on” to create a crosslinkedannulus around the periphery of the cornea. (FIG. 3.)

For the treatment of more complex corneal shape irregularities such asastigmatism, a rectangular grid pattern of LCD pixels is defined toenable the physician to define the UV irradiate zone. In one embodiment,256 rectangular pixels are defined to cover the central 8 mm of thecornea. (FIG. 4.) For astigmatism, typically some type of “butterfly”pattern of UV exposure is used to compensate for the uneven curvature ofthe astigmatic cornea. (FIG. 5.)

Control of the LCD pixels can be achieved in a number of different ways.In most embodiments, an on-lens application specific integrated circuit(ASIC) is used to receive, decode and distribute the addressing andintensity information. Specifically, the ASIC modules include auniversal asynchronous receiver transmitter (UART), a voltage regulatorand charge pump for LCD “on”/“off” control, serial data to pixel addressand intensity information converter, memory, and a self-test system. Inone embodiment consistent with Cooper '016 and '518's approach ofdelivering the UV edge light to the lens with an optical fiber, thepixel data is delivered serially over the same fiber by modulating theUV light or by supplying modulated light at a wavelength different fromthe UV light. A PIN photodiode receiver on an ASIC converts themodulated light to an electrical signal which is passed to the UART. Forsingle frequency operation, the addressing and intensity information ismodulated onto the UV light prior to initiation of the cornealtreatment, with updates to the pixel pattern delivered during any darkperiods of treatment duty cycling. For dual frequency operation, thedata is send to the LCD controller on a second optical wavelengthsimultaneously carried on the fiber and filtered from the therapeuticenergy prior to the PIN diode receiver.

In another embodiment, communication of the pixel information isaccomplished directly using electrical leads. Given the extremely lowpower requirements of LCD pixels, one version of the electricalcommunication approach is paired with a Cooper-type fiber optic lenswith 3 very fine wires loosely spiraled around the fiber carrying theUV. These leads carry: (1) the communication signal, (2) the “high”voltage, V+, and the signal and power ground or “common” voltage. Insome embodiments, the communications lead is bi-directional to enableparity checking.

The low power requirements of LCD pixels enables other embodiments foreither (or both) power or (and) information delivery via wirelesscommunications. One embodiment uses near field communications and powertransfer. In some embodiments, a loop antenna is used in the manner ofU.S. Patent Application Publication No. 2010/0103368 A1, filed Apr. 29,2010, entitled “Active Contact Lens.” In other embodiments, a fine wireantenna is brought up off the lens along the fiber optic connection;spiraled where necessary to add length to help match energy fieldfrequencies.

Although the embodiments discussed above use UV light to promotecross-linking, other embodiments of the present invention can use lightat other wavelengths effective to activate a cross-linking agent. Forexample, where riboflavin is applied to the eye as a cross-linkingagent, visible light in the blue wavelength band can be employed.

Although the invention herein has been described with reference toparticular embodiments, it is to be understood that these embodimentsare merely illustrative of the principles and applications of thepresent invention. It is therefore to be understood that numerousmodifications may be made to the illustrative embodiments and that otherarrangements may be devised without departing from the spirit and scopeof the present invention as defined by the appended claims.

The invention claimed is:
 1. An apparatus comprising: a structureadapted to rest on an anterior surface of an eye of a subject; anoptical scattering element mounted to the structure; and an thin arrayof LCD pixels mounted to the structure so that light energy can passthrough the LCD pixels to the cornea of the eye to stimulate cornealcrosslinking.
 2. The apparatus of claim 1, further comprising twoorthogonal polarizers, sandwiching the array of LCD pixels.
 3. Theapparatus of claim 1, further comprising a controller connected to theLCD pixels, the controller being operable to selectively apply voltagesto the pixels so as to control light transmission through the pixels. 4.The apparatus of claim 1 wherein the controller includes a circuitmounted on the structure.
 5. The apparatus of claim 4 further comprisingan optical fiber in optical communication with the scattering elementfor delivering light energy to the scattering element, the circuitmounted on the structure being operable to control light transmissionthrough the pixels responsive to information conveyed by modulated lighttransmitted through the fiber.
 6. The apparatus of claim 4 furthercomprising leads extending to the structure, the circuit mounted on thestructure being operable to control light transmission through thepixels responsive to information conveyed by the leads.
 7. The apparatusof claim 6 further comprising an optical fiber in optical communicationwith the scattering element for delivering light energy to thescattering element, the leads extending along the fiber.
 8. Theapparatus of claim 4 wherein the circuit mounted on the structure isoperable to control light transmission through the pixels responsive toinformation conveyed by wireless communication.
 9. The apparatus ofclaim 1 further comprising a collimator mounted on the structure. 10.The apparatus of claim 9 wherein the collimator is disposed between thescattering element and the array of pixels.
 11. The apparatus of claim 9wherein the array of pixels is disposed between the collimator and thescattering element.